Raghav Goyal - Understanding sex determination in the female germline of Drosophila melanogaster

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Johns Hopkins University
Germline sex determination is a key aspect of sexual development that allows germ cells to develop along either a male or female path to produce sperm or eggs. In most animal models, signals from surrounding somatic cells are critical for establishing germ cell sex. However, in some animals including humans and flies, the sex chromosome constitution of the germ cells is also important. Importantly, a failure to match germline and somatic sex leads to defects in gametogenesis. In Drosophila, XX males are sterile with severe germline depletion and XY females are sterile with ovarian tumors. In the presented work, we have studied how the germ cell intrinsic cues work together with extrinsic somatic cues to specify germline sex. In Drosophila, sex determination in somatic cells under the control of the switch gene Sex lethal (Sxl), which is activated in XX (female) cells. Interestingly, the loss of Sxl function in the germline results in ovarian germline tumors, a characteristic of XY (male) germ cells developing in an XX soma. Further, XY germ cells expressing Sxl produce eggs when transplanted into XX somatic gonads. These observations suggest that Sxl is both necessary and sufficient for the female identity of germ cells. The mechanism for “counting” X chromosomes to activate Sxl in XX germ cells is thought to be different from the soma. We have explored this mechanism at cis- and trans-levels. We found that Sxl’s “establishment” promoter (SxlPE) is activated in a female-specific manner in the germline, as in the soma, but that the timing of its activation, and the DNA elements that regulate it are different. Nevertheless, we find that the X chromosome-encoded gene sisterless A (sisA), which activates Sxl in the soma, is also essential for Sxl activation in the germline. Loss of sisA function leads to loss of Sxl expression in the germline, ovarian tumors, and germline loss. These defects can be rescued by Sxl, demonstrating that sisA lies upstream of Sxl in germline sex determination. We conclude that sisA acts as an X chromosome counting element in both the soma and the germline.
Sex determination, Germline, Sex lethal, sisterless A, Drosophila melanogaster